tbuckley/cabot-search huggingface dataset:
Changes in oncology pharmacy benefit drug spend and trend in the United States.
Authors: Christopher Junk, Prem R. Warde, Shanna Hoversten, Ujwal Sapkota, William Cavers, Elisea Avalos-Reyes, Kjel Andrew Johnson
Journal: Journal of Clinical Oncology (2022)

e18832 Background: The American Cancer Society projects the total cost of cancer care to increase to approximately $246 billion by 2030, an increase of roughly 34% from 2015. Estimating the nature and extent of health care spending on cancer care is vital to understanding the scope of cancer costs. Additionally, this information will help inform the development of policies and programs to optimize the value of cancer care. The purpose of this study is to evaluate changes in oncology-pharmacy benefit (PB) spend and highlight areas that may be targets for value improvement. Methods: We identified patients with cancer using medical claims data from January 1, 2019, to December 31, 2020 at a large national Medicaid, Medicare, and commercial insurer. We defined total oncology spend (TOS) as the sum of allowed costs paid for medical and pharmacy claims per year, including chemotherapy, supportive therapy, radiology, radiation, emergency room, inpatient admission and evaluation and management. We compared the total oncology spend, by type of service, for each year by cancer for patients receiving therapies paid under the PB. Results: This study included 72,923 patients in 2019 and 52,486 patients in 2020. During this time, the top 3 disease states with the highest percent of oncology spend attributed to PB were chronic myeloid leukemia (CML), multiple myeloma (MM) and chronic lymphocytic leukemia (CLL). Approximately 87% and 77% of total oncology spend were attributed to PB chemotherapy among CML and MM patients, respectively. CLL costs varied by type of insurance with 80%, 26% and 19% of the total oncology spend attributed to PB chemotherapy in Medicare, fully insured and self-insured patients, respectively. When examining year-over-year changes in PB spend from 2019 to 2020, we observed an increase in total oncology spend in gynecologic cancers regardless of the type of insurance. Additionally, we observed increases in rectal, gastric, head and neck cancers and hepatobiliary cancers primarily driven by Medicare patients. Conclusions: The economic burden of cancer is substantial and expected to significantly increase in the future. In this study, we observed differences in total oncology spend by cancer type and insurance, a proxy for age. Identifying trends in cancer spending allows the development of programs designed to better optimize value for certain tumor types.[Table: see text]
Patient-reported hope, quality of life (QOL), symptom burden, and coping mechanisms in early phase clinical trial participants.
Authors: Debra Lundquist, Andrea Pelletier, Sienna Durbin, Viola Bame, Victoria Turbini, Megan Healy, Kaitlyn Lynch, Casandra McIntyre, Dejan Juric, Betty R. Ferrell, Rachel Jimenez, Ryan David Nipp
Journal: Journal of Clinical Oncology (2022)

12114 Background: Early phase clinical trials (EP-CTs) investigate novel treatment options in oncology, with recent advances in personalized therapy leading to improved outcomes and offering hope to patients with cancer. However, little research has sought to understand associations of patient-reported hope with QOL, symptom burden, and coping mechanisms in EP-CT participants. Methods: We prospectively enrolled consecutive adults with cancer participating in EP-CTs at Massachusetts General Hospital from 04/2021-01/2022. Participants completed baseline surveys prior to treatment initiation that assessed hope (Herth Hope Index [HHI], higher scores indicate greater hope), QOL (Functional Assessment of Cancer Therapy-General), symptom burden (physical: Edmonton Symptom Assessment System [ESAS]; psychological: Patient Health Questionaire-4 [PHQ4]), and coping mechanisms (Brief COPE). We used independent samples t-test to test for mean differences between groups and regression models to explore associations of hope with patient characteristics as well as patient-reported QOL, symptom burden, and coping mechanisms. Results: Of 92 eligible patients, we enrolled 85 (enrollment rate 92.4%, median age = 61.4 years [range 54.7-68.9]; 56.5% female, and 95.3% metastatic cancer). Most common cancer types were gastrointestinal (41.2%), breast (21.2%), lung (7.1%), and gynecologic (7.1%). Patients had an average HHI score of 28.2 (range 12.0-36.0), with 32.9% reporting high levels of hope. We found that married patients had higher mean hope score compared with non-married patients (28.9 versus 26.1, p = 0.024), those with children had higher mean hope scores than those without (28.9 versus 25.9, p = 0.013), and those who had received 3 or more lines of prior therapy compared with 1-2 (29.3 versus 27.2, p = 0.045) had higher hope scores. We also found associations of hope with patients’ QOL (B = 0.24, p &lt; 0.001), symptom burden (ESAS-physical: B = -0.13, p = 0.001; PHQ4-depression: B = -2.26 p = &lt; 0.001; PHQ4-anxiety: B = -0.94, p = 0.008), and coping (self-blame [B = -1.39, p = 0.003]; acceptance [B = 1.23, p = 0.002], denial [B = -1.09, p = 0.009], support [B = 1.06, p = 0.002], active [B = 0.73. p = 0.034], disengage [B = -3.24, p &lt; 0.001]). Conclusions: In this prospective cohort study, we demonstrated that a substantial proportion of EP-CT participants had high baseline hope, and we identified several patient factors associated with their hope scores. We also found novel associations of higher hope scores with better QOL, lower symptom burden, and more adaptive coping mechanisms. Collectively, our findings highlight the potential for patient-reported hope to represent a key factor to consider when seeking to improve outcomes in EP-CT participants.
Association between molecular subtype membership or hypoxia-associated gene expression signatures and clinical outcomes in the CALGB 90601 (Alliance) phase 3 clinical trial of gemcitabine and cisplatin (GC) plus bevacizumab (B) or placebo (P).
Authors: David James McConkey, Woonyoung Choi, Susan Halabi, Bin Luo, Hikmat A. Al-Ahmadie, Jonathan E. Rosenberg, Jack Mountain, Ashley Marie Regazzi, Megan Fong, Gopa Iyer, Eliezer Mendel Van Allen, Kent William Mouw, Yujia Wen, Linda McCart, Karla V. Ballman, Himisha Beltran, Michael J. Morris
Journal: Journal of Clinical Oncology (2022)

4562 Background: Our previous work showed that basal tumors were associated with the best clinical outcomes in a Phase 2 clinical trial of neoadjuvant dose-dense MVAC plus B, and in other work we showed that basal tumors were enriched with hypoxia-associated gene expression signatures. Here we attempted to validate these findings in the C90601 Phase 3 clinical trial of GC plus B versus GC plus P. Methods: Whole transcriptome RNAseq was performed on all available tumors using Ion Torrent’s Ampliseq platform (n = 189). Tumors were assigned to molecular subtypes using 3 different classifiers - BASE47 (k=2), MDA oneNN (k=3), and the Consensus classifier (k=6). Tumor hypoxia signature enrichment was determined using 2 different gene expression signatures and gene set variation analysis (GSVA). The proportional hazards model was used to correlate molecular subtype calls and hypoxia signature enrichment with overall survival (OS) and progression-free survival (PFS) adjusting for stratification factors and treatment arm (for PFS). Results: The median OS &amp; PFS by different signatures and the hazard ratios (HR) are presented in the Table. Conclusions: Predefined signatures associated with clinical benefit in the Phase-2 neoadjuvant clinical trial were not associated with benefit in C90601. Possible explanations include the lack of strong therapeutic effects of the treatments, potential heterogeneity (“subtype plasticity”) between the profiled tissue samples and the metastatic lesions under treatment pressure, and differences in biology associated with the disease states (muscle-invasive vs advanced/metastatic disease). Support: U10CA180821, U10CA180882, Department of Defense (CA160312), Genentech; ClinicalTrials.gov Identifier: NCT00942331. [Table: see text]
A phase 1b study of unesbulin (PTC596) plus dacarbazine for the treatment of patients with locally recurrent, unresectable, or metastatic relapsed/refractory leiomyosarcoma.
Authors: Brian Andrew Van Tine, Matthew Ingham, Steven Attia, Christian Frederick Meyer, John Baird, Dhiren D'Silva, Kylie O'Keefe, Pius Maliakal, Mona M. Wahba, Marla Weetall, Gary K. Schwartz
Journal: Journal of Clinical Oncology (2022)

11507 Background: Leiomyosarcoma (LMS) is one of the most common subtypes of soft tissue sarcoma and is associated with high risk of relapse and a poor prognosis for advanced disease. In preclinical LMS models, unesbulin, a microtubule polymerization inhibitor, potentiated the activity of dacarbazine (DTIC) (Jernigan F, et al. Mol Cancer Ther. 2021;20:1846–1857). Here, we report preliminary safety and efficacy results from a Phase 1b dose escalation study evaluating the combination of unesbulin with DTIC in patients with advanced LMS (NCT03761095). Methods: In this single-arm, open-label, Phase 1b clinical trial, patients with advanced LMS received unesbulin orally at 200, 300, or 400 mg twice weekly (BIW) in combination with intravenous DTIC at 1,000 mg/m 2 once every 21 days. The primary objectives were to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of unesbulin in combination with DTIC and to characterize the safety profile of the combination. The time-to-event continual reassessment model (TITE-CRM) was used for dose finding. An expansion cohort with up to 12 additional patients is currently being enrolled. Results: As of the data cutoff on January 6, 2022, 29 LMS patients have been treated. Median prior lines of therapy were 3 (range 1–6). Of 27 evaluable patients, 12 had non-uterine and 15 had uterine LMS. The MTD/RP2D of unesbulin was determined to be 300 mg BIW with DTIC 1,000 mg/m 2 every 21 days using the TITE-CRM. At the RP2D, the most common treatment-related adverse events included fatigue, diarrhea, neutropenia, and thrombocytopenia. In the intent-to-treat population, the overall response rate (ORR) was 17.2% (5/29) and the disease control rate (DCR) (DCR = complete response + partial response + stable disease at 12 weeks) was 58.6%. At the 300 mg dose level, the ORR was 19% (4/21) and the DCR was 57.1%. Patients received a median of four cycles (range 1–12). The study is ongoing, with patients continuing to receive treatment. Conclusions: Unesbulin 300 mg BIW in combination with DTIC 1,000 mg/m 2 every 21 days was well tolerated and demonstrated promising efficacy in a heavily pre-treated patient population with advanced LMS; these results support further investigation. Updated clinical results will be presented as the data mature. A randomized, placebo-controlled, Phase 2/3 trial is planned. Clinical trial information: NCT03761095.
Genomic profile of intrahepatic cholangiocarcinoma with <i>MTAP </i>loss.
Authors: Tin-Yun Tang, Jeffrey S. Ross, Jordi Rodon Ahnert, Milind M. Javle
Journal: Journal of Clinical Oncology (2022)

4102 Background: Recent data suggests a role for immune-checkpoint inhibition in the management of intrahepatic cholangiocarcinoma (iCCA). Chromosomal 9p21 loss with CDKN2A/MTAP co-deletion commonly occurs in iCCA and may correlate with poor response to immunotherapy. Methods: 2,508 cases of intrahepatic cholangiocarcinoma underwent comprehensive genomic profiling with the FoundationOne CDx assay. PD-L1 expression was measured with IHC using the Dako 22C3 antibody and measured with the tumor proportion score (TPS) method. Prevalence of different selected genomic alterations in tumors with MTAP loss was compared against MTAP intact tumors using Fischer’s exact test. Results: In 2,508 cases analyzed, 15.5% of tumors were found to have MTAP loss. Of these, 98.7% had concomitant CDKN2A and 9p21 loss. No significant difference in immune biomarkers in MTAP loss versus wildtype (WT) was seen. PD-L1 low positive at 13.2% vs 19.2%, PD-L1 high positive at 2.9% vs 6.5%, median tumor mutational burden at 2.5 vs 2.5 and MSI high at 0.0% vs 1.6% in MTAP loss vs WT, respectively. There were no significant differences between MTAP loss and WT in potentially actionable mutations including FGFR1/2 mutations (12.4% vs 10.7%), PIK3CA (6.40% vs 6.60%), ERBB2 (4.10% vs 5.30%) and KRAS G12C (1.20% vs 1.10%) in MTAP loss vs WT, respectively. The table depicts significant genomic differences between these subgroups. Conclusions: This represents the largest iCCA cohort with MTAP loss to our knowledge. Given the historical data regarding 9p21 loss and poor response to immunotherapy, efforts targeting MTAP loss through synthetic lethality or other novel combinational therapeutics are justified.[Table: see text]
Phase 1b study of GS-3583, a novel FLT3 agonist Fc fusion protein, in patients with advanced solid tumors.
Authors: Anthony W. Tolcher, Joshua Brody, Nishanthan Rajakumaraswamy, Nehal J. Lakhani, Michelle R. Kuhne, Torsten Trowe, Deyuan Jiang, Anees Dauki, Shivaani Kummar
Journal: Journal of Clinical Oncology (2022)

2566 Background: We have previously shown that systemic administration of GS-3583, a Fms-like tyrosine kinase 3 (FLT3) agonist Fc fusion protein leads to expansion of conventional dendritic cells (cDC), both subtype 1 (cDC1) and subtype 2 (cDC2), in the periphery of healthy volunteers (Rajakumaraswamy N, et al. J Clin Oncol. 2021;39[suppl_15]:2559.). This mechanism may increase cDC in the tumor microenvironment and promote T cell mediated antitumor activity in patients with solid tumors. Methods: This ongoing, Phase 1b, open label study is investigating the safety, tolerability, immunogenicity, pharmacokinetics, and pharmacodynamics of escalating multiple doses of GS-3583 monotherapy in adult patients with advanced solid tumors using a standard 3 + 3 design. GS-3583 was administered intravenously on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle for up to 52 weeks or until progressive disease or unacceptable toxicity. Dose-limiting toxicity (DLT) was evaluated during the first 28 days of GS-3583 therapy at each dose level. Results: At the time of the Dec 3, 2021 data cut-off, 9 patients have enrolled in 3 dose escalation cohorts. Median (range) age was 71 (44-79); 4 (44%) patients were male. Tumor types were pancreatic (n=3), ovarian (n=4), and rectal (n=2). To date, no DLTs or discontinuation due to adverse events (AE) have been observed. Three patients had Grade ≥3 AEs which were also recorded as serious AEs, none of which were considered related to GS-3583. Dose dependent increase in GS-3583 exposure was observed in the evaluated dose range 2 to 12 mg with target-mediated drug disposition appearing to be saturated at doses above Dose Level 2. GS-3583 accumulation was observed at higher dose levels. GS-3583 treatment resulted in expansions of cDC1 and cDC2 at all 3 doses (Table); a dose-dependent trend in the magnitude and the durability of cDC expansion was observed. At the highest dose evaluated, GS-3583 produced ≥100-fold expansion of both cDC1 and cDC2 at multiple time points. Dose escalation on the study is still ongoing. Conclusions: GS-3583 was safe and well tolerated and induced dose-dependent expansion of cDCs in the periphery in patients with advanced solid tumors up to doses of 12 mg. These findings support further dose escalation and clinical development of GS-3583 in combination with agents that would stimulate the expanded cDCs to produce anti-tumor responses. Clinical trial information: NCT04747470. [Table: see text]
Prostate-specific membrane antigen expression in meningioma.
Authors: Heinrich Elinzano, Teddi Tubre, Sean Hacking, Abigail Alexander, Arlen Brickman, Ivana Delalle, John Donahue
Journal: Journal of Clinical Oncology (2022)

2072 Background: Meningioma is the most common CNS tumor, yet there is no effective therapy for relapsed/refractory meningioma after surgery and radiation therapy. Although most meningiomas follow a relatively benign course, some have a more aggressive course with rapid tumor growth, brain invasion, higher recurrence rates or extracranial metastasis. Prostate-specific membrane antigen (PSMA) is a transmembrane peptidase upregulated on endothelial cells of malignant solid tumors including glioblastoma and metastatic brain tumors, but not in normal vasculature. PSMA has been investigated as a therapeutic target and as a molecular imaging marker to monitor response to treatment and evaluate disease activity in PSMA-avid tumors. PSMA expression however has not been studied in meningioma. Methods: Archival tumor specimens (96 tumor samples: 58 WHO grade 1, 35 WHO grade 2, 3 WHO grade 3) from 69 patients were stained for H&amp;E, PSMA and CD31 and slides were scanned (Leica Aperio AT2 whole slide image scanner). 37 of these samples were recurrent tumors and 13 had prior radiation therapy (intensity-modulated, Gamma knife, craniospinal). 21 of the 69 patients had paired samples of initial and recurrent tumors. QuPath was utilized as open access solution to machine learning generating raw data for PSMA, CD31, PSMA/CD31 ratio and PSMA/vasculature ratio. Paired t-test, unpaired t-test and ROC curves were used for statistical analysis. Results: PSMA expression was seen in all of the study samples. PSMA expression (p = 0.0147) was lower in grade 1 compared to grade 2 and 3 tumors, but not different among histologic subtypes. PSMA/vasculature ratio (p = 0.0015) was lower in grade 1 compared to grade 2 and 3 tumors. PSMA expression (p = 0.002) and PSMA/vasculature ratio (p = 0.0015) were higher in recurrent compared to non-recurrent tumors. PSMA expression (p = 0.0442) was higher in recurrent compared to initial tumors among paired samples. When comparing initial tumors of paired samples to non-recurrent tumors, ROC curves demonstrated CD31 expression (AUC:0.7278; p = 0.0008), PSMA/CD31 ratio (AUC:0.7843; p = &lt; 0.0001) and PSMA/vasculature ratio (AUC:0.6256; p = 0.0328) to be predictors of tumor recurrence. Tumors with prior radiation therapy had higher PSMA/vascular ratio (p = 0.0439) compared to those without. Conclusions: PSMA is expressed in tumor vasculature of meningioma of any grade, increases at recurrence and persists with prior radiation therapy. Since it is present in meningioma of different grades and throughout the course of the disease, it could potentially be utilized as consistent diagnostic biomarker, relevant factor for risk of recurrence stratification and novel therapeutic target for these tumors.
Real-world experience of tyrosine kinase inhibitors in patients (pt) with recurrent bone tumours (BT): A CanSaRCC study.
Authors: Tushar Shailesh Vora, Hagit Peretz Soroka, Jonathan Christopher Noujaim, Nicolas Marcoux, Thierry Alcindor, Hatim Karachiwala, Saima Alvi, Furqan Shaikh, Albiruni Ryan Abdul Razak, Abha A. Gupta
Journal: Journal of Clinical Oncology (2022)

11530 Background: Survival after relapse in osteosarcoma (OST), Ewing Sarcoma (ES) and chondrosarcoma (CS) remains dismal. Recent reports suggest a role of tyrosine kinase inhibitors (TKI) including regorafenib (R) and cabozantinib (C). We conducted a retrospective multi-centre pan-Canadian study to assess real-word outcomes with these novel treatments in recurrent BT. Methods: After ethics approval, data from pts treated in 7 different institutions was extracted from the CanSaRCC (Canadian Sarcoma Research and Clinical Collaboration) Database. Pt characteristics, treatment and outcomes were analyzed. Response was assessed per RECIST 1.1. PFS, OS were estimated using Kaplan-Meier. TTP was defined as time from TKI start to progression. Results: From June 2018-Dec 2021, 44 pts received R or C and best response by histology are listed in Table, with an overall clinical benefit rate of 63.6%. Median time to best response was 2.3 mo (range 1 – 17). 15 pts (34.1%) required dose reduction; most common reasons were hand-foot syndrome (13.6%), mucositis (9.1%) and hypertension (9.1%). At median FU of 6.4 mo (range 1.6 – 29), 25 pts (56.8%) died, 19 (43.2%) were alive with disease (AWD). Median PFS was 4.1 mo (95%CI 2.9 – 5.7), for OST was 5.0 (N = 25, 95%CI 2.6 – 10.6), for ES was 4.1 (N = 10, 95%CI 2-5.9), and for CS 4.0 (N = 9, 1 Progressed). Median OS was 10.5 mo (95%CI 7 – 14). By univariate analysis, age, line of therapy, gender, location of primary, or R vs. C did not correlate with PFS. Conclusions: Consistent with previous published studies, our pan-country real-world analysis shows that TKI have meaningful activity in the setting of recurrent BT with acceptable toxicities. Inclusion in earlier lines of treatment and/or maintenance therapy could be questions for future research. [Table: see text]
Combining IL-12 immunocytokine (M9241) with docetaxel in metastatic prostate cancer: A phase I study.
Authors: Mohammad O. Atiq, Elias Bin Aris Chandran, Luke Meininger, Fatima Karzai, Marijo Bilusic, Jennifer L. Marte, Philip M. Arlen, Lisa M. Cordes, Julius Strauss, Jason Redman, Charalampos S. Floudas, Danielle M. Pastor, Helen Owens, Amy Hankin, Monique Williams, William Douglas Figg, William L. Dahut, Jeffrey Schlom, James L. Gulley, Ravi Amrit Madan
Journal: Journal of Clinical Oncology (2022)

e17033 Background: M9241 is an immunocytokine that targets single- and double-stranded DNA which allows the treatment to localize IL-12 to necrotic tumor (Xu, CCR 2017). M9241 was well-tolerated as a monotherapy in a Phase I study with solid tumors (Strauss J, CCR 2019). Additional preclinical data has demonstrated synergy of M9241 with cytotoxic therapy. This is the first study to examine the safety of a novel combination of chemotherapy and immunocytokines in metastatic prostate cancer. Methods: This safety analysis included patients with mCSPC or mCRPC. Patients were enrolled in a 2-dose level (DL) escalation cohort of M9241 (DL 1: 12mcg/kg, DL 2: 16.8mcg/kg) combined with docetaxel (75mg/m 2 ) with 6 patients planned per DL. A third DL of 8mcg/kg will enroll 6 more patients after the 16.8mcg/kg DL has fully enrolled. All patients were treated with ADT. Patients were initiated on treatment with docetaxel with a plan for mCSPC patients to receive six 3-week cycles of combined treatment and mCRPC patients to continue until progression or unacceptable toxicity. M9241 was given starting with the second cycle of treatment for each patient. Dose-limiting toxicity (DLT) was evaluated in the first 6 weeks after start of docetaxel (from cycle 1 day 1 through the end of the first cycle with M9241). Results: The study has enrolled 10 patients out of a planned 18 for the safety portion. Age range is 58-82 with a median of 69 years. Race distribution is 80% White and 20% Black. Gleason scores for patients were 8 (40%), 9 (40%), and 10 (20%). No DLTs were seen with either dose-level. Only 1 patient had a Grade 4 AE, neutropenia. Grade 3 toxicities included anemia, diarrhea, leukopenia, and hypotension (each occurring in 10% of the patients). The most frequent adverse events (AEs) of any grade were anemia (40%) and lymphopenia (40%), followed by fatigue (30%), diarrhea (20%), and fever (20%). Conclusions: We established a safe dose-level of M9241 at ≥ 12mcg/kg. Updated clinical data from the safety cohort (n = 18) will be presented. This demonstrates that an immunocytokine and chemotherapy can be safely combined for treatment in metastatic prostate cancer. Two planned expansion cohorts will evaluate docetaxel and M9241 in mCSPC and mCRPC, respectively. Clinical trial information: NCT04633252.